Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• undertaken. Keywords: chemical diversity; divergent cyclization; indole alkaloids; modular assembly; rhodium-catalyzed cyclization–cycloaddition; skeletal and stereochemical diversity; Introduction Biologically intriguing natural products often possess cyclic scaffolds bearing dense arrays of functional

• connection of simple building blocks, as well as divergent cyclization of a common precursor leading to distinct skeletons with complex molecular architectures. Since the naturally occurring indole alkaloids share indole and piperidine as common substructures (Figure 1b) [6], we conceived the assembly of the

• pharmacophore, based on the key features of scaffold, substructure and stereochemistry, which could be the proof of concept of our synthetic approach toward lead generation exploiting natural-product-inspired collections. (a) Biosynthetic outline of aromatic polyketides; (b) structure of indole alkaloids